Understanding the molecular mechanisms of tumorigenesis in a cancer cell is crucial to developing therapeutic approaches and to improving patient survival. It is suggested in some studies that a subset of cancer cells with high self-renewal and stemness properties, cancer stem cells (CSCs), are the key contributor to chemoradioresistance and are responsible for tumor progression as well as recurrence after conventional therapy (Bao, et al. Nature 444(7120):756-60, 2006; and Clarke, et al. Cancer Res. 66(19):9339-44, 2006). CSC-specific targeting, which could improve therapeutic efficacies and increase the patient survival rate, has become a prospective direction for cancer therapy development.
MicroRNAs (miRNAs) are a diverse family of small RNA molecules that function as a crucial post-transcriptional regulatory mechanism in various cellular functions. MicroRNAs play pivotal roles in regulating most biological processes of both normal development and various diseases, including cancer (Esquela-Kerscher and Slack. Nat Rev Cancer 6(4):259-69, 2006; and Sempere, et al. ScientificWorld Journal. 9:626-8, 2009). In tumors with downregulated or upregulated miRNAs, the use of miRNAs or anti-miRNAs, respectively, could be a therapy for inducing apoptosis and/or cell cycle arrest in cancer cells. For example, miR-26a expression is reduced in hepatocellular carcinomas, and the delivery of miR-26a using an adeno-associated virus (AAV) results in the inhibition of tumorigenesis in a murine liver cancer model (Kota, et al. Cell. 137(6):1005-17, 2009).
MicroRNA145 (miR145), is known as a tumor-suppressive miRNA, which is associated with tumor growth and metastasis in certain types of cancer (Michael, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 1(12):882-91, 2003; Iorio, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 67(18):8699-707, 2007; Iorio, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65(16):7065-70, 2005; Akao, et al. Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci. 98(12):1914-20, 2007; and Schepeler, et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 68(15):6416-24, 2008). However, it is uncertain if miR145 is involved in other cancers and cancer stem cell properties.